Skip to main content
PMC home page
Thorax logoLink to Thorax
. 1996 May;51(5):496–502. doi: 10.1136/thx.51.5.496

Relationship between the inflammatory infiltrate in bronchial biopsy specimens and clinical severity of asthma in patients treated with inhaled steroids.

J K Sont 1, J Han 1, J M van Krieken 1, C E Evertse 1, R Hooijer 1, L N Willems 1, P J Sterk 1
PMCID: PMC473594  PMID: 8711677

Abstract

BACKGROUND: Current guidelines on the management of asthma advocate the use of anti-inflammatory treatment in all but mild disease. They define disease control in terms of clinical criteria such as lung function and symptoms. However, the relationship between the clinical control of the disease and inflammation of the airways is not clear. A cross sectional study was therefore undertaken to investigate the relationship between airways inflammation and measures of clinical control and bronchial hyperresponsiveness in asthmatic patients treated with inhaled steroids. METHODS: Twenty six atopic adults (19-45 years) with mild to moderate asthma (baseline forced expiratory volume in one second (FEV1) > or = 50% predicted, concentration of histamine causing a 20% fall in FEV1 (PC20) 0.02-7.6 mg/ml) on regular treatment with inhaled steroids entered the study. Diary card recordings during the two weeks before a methacholine challenge test and bronchoscopic examination were used to determine peak flow variability, symptom scores, and use of beta 2 agonists. Biopsy specimens were taken by fibreoptic bronchoscopy from the carina of the right lower and middle lobes, and from the main carina. Immunohistochemical staining was performed on cryostat sections with monoclonal antibodies against: eosinophil cationic protein (EG1, EG2), mast cell tryptase (AA1), CD45, CD22, CD3, CD4, CD8, CD25, and CD45RO. The number of positively stained cells in the lamina propria was counted twice by using an interactive display system. RESULTS: There were no differences in cell numbers between the three sites from which biopsy specimens were taken. The PC20 for methacholine was inversely related to the average number of total leucocytes, EG1+, and EG2+ cells, mast cells, CD8+, and CD45RO+ cells in the lamina propria. These relationships were similar for each of the biopsy sites. Symptom scores, beta 2 agonist usage, FEV1, and peak flow variability were not related to any of the cell counts. CONCLUSIONS: Infiltration of inflammatory cells in the lamina propria of the airways seems to persist in asthmatic outpatients despite regular treatment with inhaled steroids. The number of infiltrating leucocytes such as mast cells, (activated) eosinophils, CD8+, and CD45RO+ cells in bronchial biopsy specimens from these patients appears to be reflected by airway hyperresponsiveness to methacholine, but not by symptoms or lung function. These findings may have implications for the adjustment of anti-inflammatory treatment of patients with asthma.

Full text

PDF
496

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ackerman V., Marini M., Vittori E., Bellini A., Vassali G., Mattoli S. Detection of cytokines and their cell sources in bronchial biopsy specimens from asthmatic patients. Relationship to atopic status, symptoms, and level of airway hyperresponsiveness. Chest. 1994 Mar;105(3):687–696. doi: 10.1378/chest.105.3.687. [DOI] [PubMed] [Google Scholar]
  2. Bentley A. M., Menz G., Storz C., Robinson D. S., Bradley B., Jeffery P. K., Durham S. R., Kay A. B. Identification of T lymphocytes, macrophages, and activated eosinophils in the bronchial mucosa in intrinsic asthma. Relationship to symptoms and bronchial responsiveness. Am Rev Respir Dis. 1992 Aug;146(2):500–506. doi: 10.1164/ajrccm/146.2.500. [DOI] [PubMed] [Google Scholar]
  3. Boulet L. P., Turcotte H., Brochu A. Persistence of airway obstruction and hyperresponsiveness in subjects with asthma remission. Chest. 1994 Apr;105(4):1024–1031. doi: 10.1378/chest.105.4.1024. [DOI] [PubMed] [Google Scholar]
  4. Bousquet J., Chanez P., Lacoste J. Y., Barnéon G., Ghavanian N., Enander I., Venge P., Ahlstedt S., Simony-Lafontaine J., Godard P. Eosinophilic inflammation in asthma. N Engl J Med. 1990 Oct 11;323(15):1033–1039. doi: 10.1056/NEJM199010113231505. [DOI] [PubMed] [Google Scholar]
  5. Bradley B. L., Azzawi M., Jacobson M., Assoufi B., Collins J. V., Irani A. M., Schwartz L. B., Durham S. R., Jeffery P. K., Kay A. B. Eosinophils, T-lymphocytes, mast cells, neutrophils, and macrophages in bronchial biopsy specimens from atopic subjects with asthma: comparison with biopsy specimens from atopic subjects without asthma and normal control subjects and relationship to bronchial hyperresponsiveness. J Allergy Clin Immunol. 1991 Oct;88(4):661–674. doi: 10.1016/0091-6749(91)90160-p. [DOI] [PubMed] [Google Scholar]
  6. Brown P. J., Greville H. W., Finucane K. E. Asthma and irreversible airflow obstruction. Thorax. 1984 Feb;39(2):131–136. doi: 10.1136/thx.39.2.131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cockcroft D. W. Therapy for airway inflammation in asthma. J Allergy Clin Immunol. 1991 May;87(5):914–919. doi: 10.1016/0091-6749(91)90412-h. [DOI] [PubMed] [Google Scholar]
  8. Djukanović R., Lai C. K., Wilson J. W., Britten K. M., Wilson S. J., Roche W. R., Howarth P. H., Holgate S. T. Bronchial mucosal manifestations of atopy: a comparison of markers of inflammation between atopic asthmatics, atopic nonasthmatics and healthy controls. Eur Respir J. 1992 May;5(5):538–544. [PubMed] [Google Scholar]
  9. Djukanović R., Roche W. R., Wilson J. W., Beasley C. R., Twentyman O. P., Howarth R. H., Holgate S. T. Mucosal inflammation in asthma. Am Rev Respir Dis. 1990 Aug;142(2):434–457. doi: 10.1164/ajrccm/142.2.434. [DOI] [PubMed] [Google Scholar]
  10. Djukanović R., Wilson J. W., Britten K. M., Wilson S. J., Walls A. F., Roche W. R., Howarth P. H., Holgate S. T. Effect of an inhaled corticosteroid on airway inflammation and symptoms in asthma. Am Rev Respir Dis. 1992 Mar;145(3):669–674. doi: 10.1164/ajrccm/145.3.669. [DOI] [PubMed] [Google Scholar]
  11. Djukanović R., Wilson J. W., Britten K. M., Wilson S. J., Walls A. F., Roche W. R., Howarth P. H., Holgate S. T. Quantitation of mast cells and eosinophils in the bronchial mucosa of symptomatic atopic asthmatics and healthy control subjects using immunohistochemistry. Am Rev Respir Dis. 1990 Oct;142(4):863–871. doi: 10.1164/ajrccm/142.4.863. [DOI] [PubMed] [Google Scholar]
  12. Djukanović R., Wilson J. W., Lai C. K., Holgate S. T., Howarth P. H. The safety aspects of fiberoptic bronchoscopy, bronchoalveolar lavage, and endobronchial biopsy in asthma. Am Rev Respir Dis. 1991 Apr;143(4 Pt 1):772–777. doi: 10.1164/ajrccm/143.4_Pt_1.772. [DOI] [PubMed] [Google Scholar]
  13. Frigas E., Motojima S., Gleich G. J. The eosinophilic injury to the mucosa of the airways in the pathogenesis of bronchial asthma. Eur Respir J Suppl. 1991 Apr;13:123s–135s. [PubMed] [Google Scholar]
  14. Hargreave F. E., Dolovich J., Newhouse M. T. The assessment and treatment of asthma: a conference report. J Allergy Clin Immunol. 1990 Jun;85(6):1098–1111. doi: 10.1016/0091-6749(90)90056-a. [DOI] [PubMed] [Google Scholar]
  15. Harper G. D., Neill P., Vathenen A. S., Cookson J. B., Ebden P. A comparison of inhaled beclomethasone dipropionate and nedocromil sodium as additional therapy in asthma. Respir Med. 1990 Nov;84(6):463–469. doi: 10.1016/s0954-6111(08)80110-2. [DOI] [PubMed] [Google Scholar]
  16. Jeffery P. K., Godfrey R. W., Adelroth E., Nelson F., Rogers A., Johansson S. A. Effects of treatment on airway inflammation and thickening of basement membrane reticular collagen in asthma. A quantitative light and electron microscopic study. Am Rev Respir Dis. 1992 Apr;145(4 Pt 1):890–899. doi: 10.1164/ajrccm/145.4_Pt_1.890. [DOI] [PubMed] [Google Scholar]
  17. Kerstjens H. A., Brand P. L., Hughes M. D., Robinson N. J., Postma D. S., Sluiter H. J., Bleecker E. R., Dekhuijzen P. N., de Jong P. M., Mengelers H. J. A comparison of bronchodilator therapy with or without inhaled corticosteroid therapy for obstructive airways disease. Dutch Chronic Non-Specific Lung Disease Study Group. N Engl J Med. 1992 Nov 12;327(20):1413–1419. doi: 10.1056/NEJM199211123272003. [DOI] [PubMed] [Google Scholar]
  18. Kirby J. G., Hargreave F. E., Gleich G. J., O'Byrne P. M. Bronchoalveolar cell profiles of asthmatic and nonasthmatic subjects. Am Rev Respir Dis. 1987 Aug;136(2):379–383. doi: 10.1164/ajrccm/136.2.379. [DOI] [PubMed] [Google Scholar]
  19. Laitinen L. A., Laitinen A., Haahtela T. A comparative study of the effects of an inhaled corticosteroid, budesonide, and a beta 2-agonist, terbutaline, on airway inflammation in newly diagnosed asthma: a randomized, double-blind, parallel-group controlled trial. J Allergy Clin Immunol. 1992 Jul;90(1):32–42. doi: 10.1016/s0091-6749(06)80008-4. [DOI] [PubMed] [Google Scholar]
  20. Laitinen L. A., Laitinen A., Haahtela T. Airway mucosal inflammation even in patients with newly diagnosed asthma. Am Rev Respir Dis. 1993 Mar;147(3):697–704. doi: 10.1164/ajrccm/147.3.697. [DOI] [PubMed] [Google Scholar]
  21. O'Connor G. T., Sparrow D., Weiss S. T. A prospective longitudinal study of methacholine airway responsiveness as a predictor of pulmonary-function decline: the Normative Aging Study. Am J Respir Crit Care Med. 1995 Jul;152(1):87–92. doi: 10.1164/ajrccm.152.1.7599868. [DOI] [PubMed] [Google Scholar]
  22. Park C. S., Lee S. M., Uh S. T., Kim H. T., Chung Y. T., Kim Y. H., Choi B. W., Hue S. H., Lee H. B. Soluble interleukin-2 receptor and cellular profiles in bronchoalveolar lavage fluid from patients with bronchial asthma. J Allergy Clin Immunol. 1993 Feb;91(2):623–633. doi: 10.1016/0091-6749(93)90268-k. [DOI] [PubMed] [Google Scholar]
  23. Pattemore P. K., Holgate S. T. Bronchial hyperresponsiveness and its relationship to asthma in childhood. Clin Exp Allergy. 1993 Nov;23(11):886–900. doi: 10.1111/j.1365-2222.1993.tb00273.x. [DOI] [PubMed] [Google Scholar]
  24. Quanjer P. H., Tammeling G. J., Cotes J. E., Pedersen O. F., Peslin R., Yernault J. C. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl. 1993 Mar;16:5–40. [PubMed] [Google Scholar]
  25. Rijcken B., Schouten J. P., Xu X., Rosner B., Weiss S. T. Airway hyperresponsiveness to histamine associated with accelerated decline in FEV1. Am J Respir Crit Care Med. 1995 May;151(5):1377–1382. doi: 10.1164/ajrccm.151.5.7735588. [DOI] [PubMed] [Google Scholar]
  26. Robinson D. S., Bentley A. M., Hartnell A., Kay A. B., Durham S. R. Activated memory T helper cells in bronchoalveolar lavage fluid from patients with atopic asthma: relation to asthma symptoms, lung function, and bronchial responsiveness. Thorax. 1993 Jan;48(1):26–32. doi: 10.1136/thx.48.1.26. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sterk P. J., Bel E. H. Bronchial hyperresponsiveness: the need for a distinction between hypersensitivity and excessive airway narrowing. Eur Respir J. 1989 Mar;2(3):267–274. [PubMed] [Google Scholar]
  28. Trigg C. J., Manolitsas N. D., Wang J., Calderón M. A., McAulay A., Jordan S. E., Herdman M. J., Jhalli N., Duddle J. M., Hamilton S. A. Placebo-controlled immunopathologic study of four months of inhaled corticosteroids in asthma. Am J Respir Crit Care Med. 1994 Jul;150(1):17–22. doi: 10.1164/ajrccm.150.1.8025745. [DOI] [PubMed] [Google Scholar]
  29. Waalkens H. J., van Essen-Zandvliet E. E., Gerritsen J., Duiverman E. J., Kerrebijn K. F., Knol K. The effect of an inhaled corticosteroid (budesonide) on exercise-induced asthma in children. Dutch CNSLD Study Group. Eur Respir J. 1993 May;6(5):652–656. [PubMed] [Google Scholar]
  30. Walker C., Kaegi M. K., Braun P., Blaser K. Activated T cells and eosinophilia in bronchoalveolar lavages from subjects with asthma correlated with disease severity. J Allergy Clin Immunol. 1991 Dec;88(6):935–942. doi: 10.1016/0091-6749(91)90251-i. [DOI] [PubMed] [Google Scholar]
  31. Wardlaw A. J., Dunnette S., Gleich G. J., Collins J. V., Kay A. B. Eosinophils and mast cells in bronchoalveolar lavage in subjects with mild asthma. Relationship to bronchial hyperreactivity. Am Rev Respir Dis. 1988 Jan;137(1):62–69. doi: 10.1164/ajrccm/137.1.62. [DOI] [PubMed] [Google Scholar]
  32. Whyte M. K., Choudry N. B., Ind P. W. Bronchial hyperresponsiveness in patients recovering from acute severe asthma. Respir Med. 1993 Jan;87(1):29–35. doi: 10.1016/s0954-6111(05)80310-5. [DOI] [PubMed] [Google Scholar]
  33. Woolcock A. J., Jenkins C. R. Assessment of bronchial responsiveness as a guide to prognosis and therapy in asthma. Med Clin North Am. 1990 May;74(3):753–765. doi: 10.1016/s0025-7125(16)30550-8. [DOI] [PubMed] [Google Scholar]
  34. Woolcock A. J., Yan K., Salome C. M. Effect of therapy on bronchial hyperresponsiveness in the long-term management of asthma. Clin Allergy. 1988 Mar;18(2):165–176. doi: 10.1111/j.1365-2222.1988.tb02856.x. [DOI] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES